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眼内压升高与大鼠视网膜细胞凋亡及一氧化氮合酶免疫反应性增加有关,而视网膜源性舒张因子的有效性未受影响。

The elevation of intraocular pressure is associated with apoptosis and increased immunoreactivity for nitric oxide synthase in rat retina whereas the effectiveness of retina derived relaxing factor is unaffected.

作者信息

Takır Selçuk, Gürel-Gürevin Ebru, Toprak Ayça, Demirci-Tansel Cihan, Uydeş-Doğan B Sönmez

机构信息

Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey; Department of Medical Pharmacology, Section of Internal Medical Sciences, Faculty of Medicine, Giresun University, Giresun, Turkey.

Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey.

出版信息

Exp Eye Res. 2016 Apr;145:401-411. doi: 10.1016/j.exer.2016.03.002. Epub 2016 Mar 4.

Abstract

Glaucoma is a progressive ocular disease that stands in the upper rank for the cause of blindness in worldwide. In the present study, we aimed to elucidate the possible disturbances occurred in the layers of retina due to an increase in intraocular pressure (IOP) and to verify the effectiveness of retina derived relaxing factor, i.e., RRF in this pathologic condition. The increase in IOP was induced by cauterization of the three of episcleral veins simultaneously in rats. After 8 weeks period, the retinas excised from the vein cauterized eyes were evaluated for the possible histopathological and ultrastructural alterations as well as for the relaxing effects on isolated bovine retinal and rat mesenteric arteries, in comparison with the retinas obtained from contralateral sham-operated eyes. In the retinas of IOP-elevated eyes, profound morphological deteriorations were determined in the ganglion and outer nuclear cell layers which were associated with an increased number of TUNEL positive cells in the ganglion and inner nuclear cell layers. Increased immunohistochemical stainings for three isoforms of nitric oxide synthase (NOS) were defined in almost all layers of the retinas of IOP-elevated eyes, in which eNOS was abundant particularly in the inner plexiform and ganglion cell layers. An irregular basal folding of retinal pigment epithelium (RPE) and an increased inter lamellar space of photoreceptor cell layer furtherly characterized the prominent degeneration of those layers in the retinas of IOP-elevated eyes. On the other hand, the relaxing effects of the retina obtained from IOP-elevated eyes were determined to be unchanged on the retinal and mesenteric arteries precontracted either with prostaglandin F2α (PGF2α, 30 μM) or potassium chloride (K(+), 100 mM), when compared with the relaxations of control retina obtained from contralateral sham-operated eyes. Overall, these findings suggested that the elevation of IOP induces prominent structural changes in rat retina particularly in the ganglion and inner layers that is associated with marked apoptosis and increased immunoreactivity for NOS, while the functional effectiveness of retina derived relaxing factor, i.e., RRF is unaffected.

摘要

青光眼是一种进行性眼部疾病,在全球致盲原因中位居前列。在本研究中,我们旨在阐明由于眼内压(IOP)升高而在视网膜各层中可能发生的紊乱,并验证视网膜衍生的舒张因子,即RRF在这种病理状态下的有效性。通过同时烧灼大鼠的三条巩膜静脉来诱导IOP升高。8周后,与对侧假手术眼获得的视网膜相比,对从静脉烧灼眼切除的视网膜进行评估,以观察可能的组织病理学和超微结构改变,以及对分离的牛视网膜和大鼠肠系膜动脉的舒张作用。在IOP升高的眼中,视网膜的神经节和外核细胞层出现了严重的形态学恶化,这与神经节和内核细胞层中TUNEL阳性细胞数量增加有关。在IOP升高的眼中,几乎所有视网膜层中一氧化氮合酶(NOS)三种同工型的免疫组化染色均增加,其中eNOS尤其在内部神经纤维层和神经节细胞层中丰富。视网膜色素上皮(RPE)的基底折叠不规则以及光感受器细胞层的层间间隙增加,进一步表明IOP升高的眼中这些层的显著退化。另一方面,与从对侧假手术眼获得的对照视网膜的舒张作用相比,发现从IOP升高的眼中获得的视网膜对用前列腺素F2α(PGF2α,30μM)或氯化钾(K(+),100mM)预收缩的视网膜和肠系膜动脉的舒张作用未发生变化。总体而言,这些发现表明IOP升高会诱导大鼠视网膜特别是神经节和内层出现显著的结构变化,这与明显的细胞凋亡和NOS免疫反应性增加有关,而视网膜衍生的舒张因子即RRF的功能有效性未受影响。

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